The present invention relates to intravascular drug delivery devices which permit the administration of a drug directly to the inner wall of a tubular body vessel.
Percutaneous transluminal coronary angioplasty (PTCA) has been very effective for treating intravascular stenoses within coronary arteries and peripheral arteries. In this procedure a dilation catheter is advanced over a guide wire into the femoral or other access artery and advanced therein until the flexible, relatively inelastic balloon on the distal tip of the catheter is properly positioned within the stenotic vessel across the lesion to be dilated. The balloon is then inflated to a predetermined size with a radiopaque liquid at relatively high pressures to radially compress the stenotic lesion against the inside of the artery wall to thereby increase the luminal diameter of the stenotic vessel. The balloon is then deflated so that the dilation catheter can be removed and blood flow resumed through the stenotic vessel.
Although PTCA has proved to be an effective alternative to surgical intervention, the clinical results of angioplasty treatment include endothelial denudation, vascular wall damage, and rupture of the tunica intima vasorum. These injuries stimulate a number of growth processes, resulting in a high incidence of proliferation of arterial smooth muscle cells, with a resulting restenosis.
It is known that certain drugs, most notably heparin, are effective in reducing the reformation of certain types of stenotic lesions in animal models. Generally, these drugs show a tendency to inhibit smooth muscle cell proliferation. However, it is generally not desirable that these drugs be injected as a bolus dose to be carried to the site of the lesion, primarily due to the undesirable side effects caused by the relatively large dosage required. Therefore, it is desirable to administer these drugs directly to the lesion, so that a significantly smaller dosage may be employed and the side effects minimized.
One method for administering plaque-inhibiting drugs directly on stenotic lesions, disclosed in U.S. Pat. No. 4,824,436, issued to Wolinsky, utilizes a catheter having a main catheter body with a drug delivery conduit and a balloon expansion conduit therein. The catheter body is held in place by the inflation of two spaced balloons, one at the proximal end of the plaque body and the other at the distal end. The two balloons are inflated by forcing fluid through the balloon expansion conduit, thereby holding the catheter body in place and forming a drug-receiving chamber in the artery. Once the catheter is in place, a drug is forced through the central conduit and into the arterial chamber, whereupon the drug adheres to and penetrates the adjacent arterial tissue.
A problem with this arrangement is that the drug is administered through only a single opening in the catheter, so that the formation of a drug-receiving chamber is necessary to allow the drug to contact the entire lesion Burface. If the restenotic lesion occurs at a branched portion of a blood vessel, the balloons would be unable to form an enclosed chamber to prevent the drug from flowing downstream through the branched vessel.
A second device is disclosed in U.S. Pat. No. 4,994,033, issued to Shockey, et al. In this device, three elongated, flexible, delivery tubes are concentrically disposed relative to one another. Two expandable balloons or sleeves are located at the distal ends of the tubes. The outer drug delivery sleeve, which includes a pattern of micro-apertures therein, has its proximal end secured to the outer tube, and its distal end secured to the inner expander sleeve. The proximal end of the inner expander sleeve is attached to the intermediate tube, and the distal end is bonded to the innermost tube. Essentially, the drug is first introduced into the outer tube and into the drug delivery tube at a pressure generally insufficient to eject the drug out of the micro-apertures. Next, the inflation fluid is introduced through the intermediate tube and into the expander sleeve. As the pressure is increased within the expander sleeve causing it to expand, the drug is simultaneously forced through the micro-apertures to contact the lesion with the drug.
A problem with this catheter is that the outer sleeve cannot be expanded against the lesion absent an infusion pressure to the inner expander sleeve. Therefore, it would be difficult to control the amount of pressure exerted against the arterial wall. In addition, it would be difficult to control the amount of drug that is released through the micro-apertures, since the steps of balloon expansion and drug delivery occur simultaneously. In particular, there is opportunity for a significant loss of drug into the bloodstream both during injection of the drug into the outer sleeve and subsequent inflation of the inner sleeve, thereby causing expansion of the outer drug delivery sleeve that has already been injected with the drug. In addition, the interface between the inner and outer sleeves may cause resistance to injection of the drug through the micro-apertures upon inner sleeve expansion.
Yet another problem of the catheter device disclosed in Shockey, et al. is that an unequal distribution of drug is likely to occur upon delivering the drug to a stenotic lesion located at a branched arterial passageway. The distal end of the catheter positioned in the passageway has a low pressure side located toward the branched vessel and an opposite high pressure side. As the inner sleeve is expanded by the inflation fluid, drug is forced out through the micro-apertures in the outer sleeve. Since fluids take the path of least resistance, and since at least some of the drug is forced out of the outer sleeve during inflation of the expander sleeve, a significant amount of the drug is likely to be delivered out the low pressure side of the outer sleeve toward the branched vessel, leaving an insufficient supply of the drug delivered to the portion of the lesion adjacent the high pressure side of the outer sleeve.
A catheter having an expandable stent is disclosed in U.S. Pat. No. 5,002,560, issued to Machold, et al. The catheter assembly includes an expandable wire cage or stent that is formed by a plurality of spirally-arranged strands. The cage is radially expanded and contracted by a core member or guide wire that is disposed within an elongated catheter body. The proximal end of the assembly includes a manipulator, which includes an internally threaded cap and a torquing member. Rotation of the cap causes longitudinal movement of the externally threaded member, thereby moving the torquing member, which moves the guide wire attached thereto. Movement of the guide wire changes the axial spacing between the ends of the expandable cage, and thus the radial dimension of the cage.
This catheter assembly has performed effectively to maintain the patency of a blood vessel for a long period of time after a vascular procedure as well as to allow the perfusion of blood through the blood vessel while the blood vessel is held open. It is now desired to utilize some of these concepts in improving upon the drug delivery catheters of the prior art.